Epigenetic and Biobehavioral Determinants of Preterm Birth in Black Women

描述（由申请人提供）：早产（PTB，妊娠37周之前出生）是婴儿死亡的主要原因。在已知的PTB风险因素中，最强的是非洲裔美国人（AA）种族。与白人相比，AA女性患PTB的风险是白人的1.5倍（16.8%对10.5%）。拟议的研究将调查与PTB相关的特定生物行为因素是否影响基因的表观遗传调控，以促进AA女性的PTB。这项研究将有助于对PTB种族内风险的生物心理社会了解，提供与AA女性相关的重要风险和保护因素的见解。拟议的研究与消除种族差异的框架是一致的，该框架认识到需要研究种族内的风险作为重要的第一步，并且与国家少数民族健康和健康差异研究所的目标一致，即促进对不成比例地影响健康差异人群的条件所涉及的生物机制的理解。 评估表观遗传机制介导特定生物行为因素与AA妇女PTB之间关系的假设，这项研究将利用正在进行的AA妇女早产纵向研究的生物行为和生物学数据（R 01 NR 014800）正在招募一个社会经济多样化的H 960 AA孕妇队列，并在产前护理预约期间收集数据（妊娠10-14周和26-30周）和分娩时。使用巢式病例对照方法，病例被指定为经历PTB的患者（估计125例），对照被指定为经历足月分娩的患者。基于这项研究设计，我们将：（1）描述早产和足月分娩的AA妇女在妊娠过程中PBMC DNA甲基化和RNA表达模式的特征;（2）确定影响外周DNA甲基化和RNA表达模式的生物行为因素，包括营养状况、压力、生殖道感染;（3）评估PTB与AA妇女中DNA甲基化和RNA表达之间的关联，这些关联独立于生物行为因素;（4）确定这些表观遗传差异是否可以在妊娠中期和/或晚期检测到。这项研究的成功得到了临床医生、基础和翻译科学家的多学科合作的支持，这些科学家代表了产科结局和母婴健康、遗传学和表观遗传学、营养、压力、流行病学和信息学方面的专业知识;拟议研究的关键人员与正在进行的R 01“黑人妇女微生物组和早产的生物行为决定因素”重叠;埃默里大学临床和转化科学研究所（CTSA奖# NIH UL 1 TR 000454）的支持。最后，亚特兰大是家庭对AA妇女广泛的社会经济地位谁是由埃默里大学的附属交付医院服务，允许足够的变化，在研究中的生物行为因素，以区分独立和相互作用的影响DNA甲基化，并最终对PTB的风险。

DESCRIPTION (provided by applicant): Preterm birth (PTB, birth prior to 37 weeks' gestation) is a leading cause of infant mortality. Of the known risk factors for PTB, among the strongest is African American (AA) race. Compared to Caucasians, AA women have more than 1.5 times the risk of PTB (16.8% vs. 10.5%). The proposed research will investigate whether specific bio behavioral factors linked to PTB influence the epigenetic regulation of genes to promote PTB in AA women. This research will contribute to a bio psychosocial understanding of within-race risk for PTB, providing insight into important risk and protective factors relevant to AA women. The proposed research is consistent with frameworks for eliminating racial disparities, which recognize the need to study risks within-race as a vital first step, and is congruent with the National Institute of Minority Health and Health Disparities goal of promoting understanding of the biological mechanisms involved in conditions that disproportionately affect health disparity populations. To evaluate the hypothesis that epigenetic mechanisms mediate the relationship between specific bio behavioral factors and PTB for AA women, the proposed study will leverage bio behavioral and biologic data from an on-going longitudinal study of preterm birth in AA women (R01 NR014800) that is enrolling a socioeconomically diverse cohort of H 960 pregnant AA women and collecting data during prenatal care appointments (at 10-14 and 26-30 weeks' gestation) and at delivery. Using a nested case-control approach, cases are designated as those who experience PTB (an estimated 125 cases) and controls as those who experience a term birth. Building from this study design, we will: (1) characterize PBMC DNA methylation and RNA expression patterns over the course of pregnancy among AA women who deliver preterm and at term; (2) identify bio behavioral factors - including nutritional status, stress, an reproductive tract infections - that influence patterns of peripheral DNA methylation and RNA expression; (3) evaluate associations between PTB and both DNA methylation and RNA expression among AA women that are independent of the bio behavioral factors and (4) determine whether these epigenetic differences can be detected in the second and/or third trimester. The success of this research is supported by a multidisciplinary collaboration of clinicians, basic and translational scientists representing expertise in obstetrical outcomes and maternal-child health, genetics and epigenetics, nutrition, stress, epidemiology and informatics; the overlap of key personnel for the proposed study and the on-going R01 'Bio behavioral Determinants of the Micro biome and Preterm Birth for Black Women'; and support from Emory University's Clinical and Translational Science Institute (CTSA award # NIH UL1TR000454). Finally, Atlanta is home to AA women of broad socioeconomic status who are served by Emory's affiliated delivery hospitals, allowing for sufficient variation in the bio behavioral factrs under study to distinguish independent and interactive effects on DNA methylation and, ultimately, on the risk of PTB.